Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, California, USA.
Proteomics Clin Appl. 2024 Nov;18(6):e202300236. doi: 10.1002/prca.202300236. Epub 2024 Jul 28.
Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Liver tissue and plasma samples were collected during liver biopsy to diagnose MASLD. Untargeted proteomics was performed on 64 patients.
Twenty plasma proteins were up- or downregulated in patients with MASH compared with those without MASH. The potential biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These 10 plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values.
The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.
基于来自血浆和肝组织的蛋白质组学和脂质组学数据，已经考虑了代谢功能障碍相关脂肪性肝炎（MASH）的生物标志物，但没有临床获益。本研究评估了同时从代谢功能障碍相关脂肪性肝病（MASLD）患者中采集的基于蛋白质组学的血浆和肝组织生物标志物。
在进行肝活检以诊断 MASLD 时采集肝组织和血浆样本。对 64 名患者进行了非靶向蛋白质组学分析。
与无 MASH 的患者相比，MASH 患者的 20 种血浆蛋白上调或下调。利用这些血浆蛋白最佳组合的潜在生物标志物，其用于检测 MASH 的受试者工作特征曲线（AUROC）下面积为 0.671，与无 MASH 的患者相比。然而，在 MASH 患者中，无显著调节的肝组织蛋白中未发现这 20 种血浆蛋白。其中 10 种在 MASLD 进展的肝组织中表现出趋势和相关性。这 10 种血浆蛋白的 MASH 识别 AUROC 为 0.793，且具有更高的阳性和阴性预测值。
MASH 患者的血浆和肝组织蛋白表达不能直接比较。在肝组织中也有表达的血浆蛋白生物标志物有助于提高 MASH 的检测能力。
